An internal adsorbent can adsorb toxic substances taken into a body and harmful substances metabolized in a body, in the gastrointestinal tract, and can excrete them to the outside of the body. As an example of the internal adsorbent, an oral adsorbent which can be orally administered to cure a disorder of renal and liver functions has been developed and used effectively (Patent literature 1). This adsorbent for oral administration comprises a porous spherical carbonaceous substance having particular functional groups (i.e. a surface-modified spherical activated carbon); having a high degree of safety and stability in the body; and having a useful selective adsorbability, that is, an excellent adsorbability of harmful substances in the presence of bile acid in an intestine, and a low adsorbability of useful substances such as digestive enzymes in the intestine. For these reasons, the adsorbent for oral administration is widely and clinically used for patients suffering from disorders of the liver or renal function, as an adsorbent having few side effects such as constipation. The above adsorbent for oral administration disclosed in Patent literature 1 was prepared by forming a spherical activated carbon from a pitch such as a petroleum pitch as a carbon source, and then carrying out an oxidizing treatment and a reducing treatment. Recently, as described in Patent literature 2, an adsorbent for oral administration prepared from a thermosetting resin such as phenol resin as a carbon source has been developed. The adsorbent for oral administration disclosed in Patent literature 2 has excellent selective adsorbability compared to the adsorbent for oral administration disclosed in Patent literature 1. Further, it is important that an adsorbent for oral administration can adsorb as much of the toxic substances as possible during the retention period from the oral administration to excretion. According to descriptions of Patent literatures 3 and 4, the adsorbent for an oral administration comprising a spherical activated carbon having smaller average particle size can adsorb many toxins within the retention period from the oral administration to excretion.
It is known that the adsorbability of the internal adsorbent is reduced by adsorbing moisture in the atmosphere. In order to prevent the reduction of the adsorbability, it is necessary to store in a tight container. According to the definition in the Japanese Pharmacopoeia, a tight container means a container wherein an invasion of a liquid and solid contaminant or water can be protected in usual handling or usual state of conservation, and medicine therein can be protected from loss, efflorescence, deliquescence, or vaporescence. The tight container, for example, may be a tube, can, single-dose package, plastic container, or the like. As embodiments of package capable of tight-packing the internal adsorbent, there may be mentioned: can package, bottle package using cap with packing, single-dose package such as three sided-sealed package, four-sided sealed package, stick package, and the like. In particular, the single-dose package is a superior embodiment of package, as one dose of internal adsorbent to be administered can be packed.
The single-dose package containing an internal adsorbent may be prepared by tight-packing internal adsorbent into a composite film having a sealant layer on its inner surface. A packaging material with sealant layer which may be used for the single-dose package containing internal adsorbent is disclosed, for example, in Patent literature 5 by the present inventors. For example, the single-dose package containing an internal adsorbent is shown in FIG. 1. That is, a single-dose package containing an internal adsorbent having heat-sealed region and open region can be prepared by filling the internal adsorbent to a stick consisting of composite film, and sealing an upper portion of the stick by heat.
The internal adsorbent has a property of adsorbing and desorbing air, in addition to the essential property of adsorbing the toxic substances. Air adsorbed in the internal adsorbent can be desorbed or released therefrom by raising the temperature in the surrounding environment. Further, air adsorbed in the internal adsorbent can be desorbed or released therefrom by reducing the pressure in the surrounding environment. This property of the internal adsorbent is reversible. That is, air is adsorbed in the internal adsorbent by lowering the temperature or by increasing the pressure in the surrounding environment. Therefore, when a single-dose package, which is tight-packed at low temperature, is placed at high temperature, air adsorbed in the internal adsorbent is desorbed or released, and the volume of the single-dose package containing the internal adsorbent expands. Therefore, there is a high possibility that problems, such as a break in seal region, a break of the package, or a pinhole formation, will arise due to the volume expansion of the single-dose package. Further, problems in storage and delivery thereof may arise due to the volume expansion of the single-dose package. In order to avoid the above problems, a method for filling the internal adsorbent, wherein the internal adsorbent is filled at temperature of 5° C. higher than room temperature to 300° C., or under reduced pressure, is carried out. According to the above method, air contained in the internal adsorbent is released just before packaging. And then, when the temperature of the internal adsorbent drops after tight-packing the internal adsorbent into the packaging material of the single-dose package, air in the single-dose package is adsorbed by the internal adsorbent therein. As a result, the pressure in the single-dose package containing the internal adsorbent is reduced, and the single-dose package becomes a vacuum-pack shaping a flattened single-dose package. The volume of the single-dose package obtained by the above method does not expand, when the temperature therearound is high. This is because, little air is released from the internal adsorbent (Patent literature 6).